JPH07101866A - Intraperitoneal adhesion inhibitor - Google Patents

Abstract

PURPOSE:To obtain intraperitoneal adhesion inhibitor which contains xanthane gum as an active ingredient and can prevent intestines from adhering to each other or occluding to keep postoperative patients well. CONSTITUTION:The adhesion inhibitor includes xanthane gum, as an active ingredient, which is a microorganism-originating high-molecular-weight polysaccharide produced by Xanthomonas campestris. After celiotomy, the inhibitor is intraperitoneally poured to cover the operated site in an amount of 10 to 200ml. The adhesion inhibitor can contain medically active components, when needed, other than the gum. The intraperitoneal adhesion caused by tissue drying and bleeding on operation and by tissue damages accompanied surgery operation can be prevented. The xanthane gum is usually prepared into high viscous aqueous solution of 0.1 to 1.0W/V% concentration.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an intraperitoneal adhesion preventive agent containing xanthan gum as an active ingredient.

[0002]

2. Description of the Related Art Although the adhesion of the intestinal tract, which occurs after laparotomy and particularly during gastrointestinal surgery, tends to decrease with the improvement of surgical techniques and equipment, it is the current situation that it cannot be completely prevented, which is a nuisance to surgeons. It's a big problem. In the field of gynecology, postoperative adhesions may also be accompanied by infertility due to oviduct obstruction and sometimes intestinal obstruction. Intraperitoneal adhesions do not always cause disability, but they may cause adhesive ileus, resulting in reoperation and worsening the prognosis of postoperative patients (Maegoshi Masamitsu et al., Surgical Treatment, 68, 1005 (1993). )).

[0003] Adhesion is a result of a mechanism of tissue repair by an inflammatory reaction as one of biological defense reactions, and is triggered by damage to the intestinal serosa or peritoneum. After receiving various stimuli, shedding of damaged serosa, exudation of fibrinogen, and fibrin deposition by the same mechanism as blood coagulation, and finally formation of fibrinous fusion with nearby tissues by the involvement of fibroblasts This is believed to be the case (Osamu Sugimoto, Obstetrics and Gynecology, 53, 185 (1986)). At present, a method for preventing such adhesion has not been established, and attempts have been made to use various drugs and special membranes. As a drug to prevent adhesion, one that has a wound surface covering action centered on polymeric substances,
For example, sodium alginate (JP-A-57-1679)
19), sodium chondroitin sulfate (Oelsne
r G. et al., J. Reprod. Med., 32, 812 (1987)) and sodium hyaluronate (Urman B. et al., Fertil. Ster.
il, 56, 563 (1991)) and other high molecular weight polysaccharides have been found to be effective. Others, such as fibrinolytic substances and steroids, have been tried and some have been clinically used. However, it is difficult to say that all of them are effective.

[0004]

An object of the present invention is to provide an excellent intraabdominal adhesion preventive agent.

[0005]

[Means for Solving the Problems] In view of the above situation, the present inventors have conducted extensive studies on high molecular weight polysaccharides, and as a result, found that xanthan gum has an anti-adhesion effect superior to previously reported substances,
The present invention has been completed.

That is, the present invention relates to an intraabdominal adhesion preventive agent containing xanthan gum as an active ingredient.

In the present invention, xanthan gum is a polymeric polysaccharide of microbial origin produced by Xanthomonas campestris, which contains D-glucose, D-mannose and D-glucuronic acid as constituent sugars, and pyruvic acid and acetic acid. And potassium. It has a molecular weight of 2-15 million and is soluble in water, and its aqueous solution forms a hydrophilic colloid. Further, it is excellent in pH stability, acid resistance, alkali resistance, heat resistance, etc., and tasteless and odorless, so that it is often used as a thickening stabilizer and emulsifier for foods. The present inventors have completed the present invention from a completely new finding that intraperitoneal adhesion is prevented by administering an aqueous xanthan gum solution intraperitoneally after laparotomy.

The xanthan gum in the agent for preventing intra-abdominal adhesion of the present invention is usually prepared as an aqueous solution having a high viscosity of 0.1 to 1.0 W / V%. As the solvent, a physiological saline solution or a suitable electrolyte solution, for example, JP-A-2-3040 shown in Table 1 is used.
It is desirable to use the peritoneal lavage fluid (Table 1) described in Japanese Patent No. 26.

[0009]

[Table 1]

The intraabdominal adhesion-preventing agent of the present invention is used after laparotomy.
It is preferably injected intraperitoneally and applied to cover the surgical site. The injection volume may be appropriately selected according to the age, body weight, sex difference, symptom and intra-abdominal injury area, and preferably in the range of 10 to 200 ml.

If desired, the agent for preventing intra-abdominal adhesion in the present invention may contain other medicinal components in addition to xanthan gum.

[0012]

EXAMPLES The present invention will be described in detail below with reference to Examples and Test Examples conducted for the agent for preventing intra-abdominal adhesion of the present invention.

[Example 1] 10 g of xanthan gum is shown in Table 1.
Was added to the peritoneal lavage solution having the composition shown in (3) and dissolved by stirring at room temperature for 3 to 4 hours. After the solution became uniform, the total amount of the peritoneal lavage solution was adjusted to 1000 ml to obtain the intended 1.0% intraabdominal adhesion inhibitor. A physiological saline solution may be used instead of the peritoneal lavage solution.

[Examples 2 to 4] In the same manner as in Example 1,
Xanthan gum concentration 0.02% (Example 2), 0.1%
(Example 3) and 0.5% (Example 4) of each concentration of the intraperitoneal adhesion inhibitor were obtained.

[Comparative Solution 1] The peritoneal lavage fluid shown in Table 1 above was used as Comparative Solution 1.

[Comparative Solution 2] For comparison, sodium hyaluronate was used as a polymeric polysaccharide for which an adhesion preventing effect was reported. That is, in the same manner as in Example 1, 5 g of sodium hyaluronate was used instead of xanthan gum to obtain the intended comparative liquid 2.

[Test Example] The following adhesion model was prepared using male SD rats of 10 to 13 weeks of age. That is, under anesthesia with pentobarbital, a laparotomy was performed from the part about 3 cm from the xiphoid process to the lower part along the midline for about 4 cm, the epididymal fat on the left and right was removed, and then 10 parts from the ileocecal part to the oral side with dry gauze.
The ileum up to cm was rubbed 9 times (to the extent that bleeding was observed). After that, 10 ml of each intraabdominal adhesion preventive agent of Examples 1 to 4 containing a predetermined concentration of xanthan gum was injected into the abdominal cavity, and the abdomen was closed by double-layer suture. One week after the laparotomy, the state of intestinal adhesion was evaluated. Adhesion was evaluated by measuring the length of adhesion (adhesion length) of other intestinal tracts (jejunum, cecum, large intestine, etc.) to and from the treated ileum. Similarly, the control group was injected intraperitoneally with 1, 10 ml of the comparative solution, and the positive control group was intraperitoneally injected with 2, 10 ml of the comparative solution. The results are shown in Table 2.

[0018]

[Table 2]

From Table 2, xanthan gum exhibited a good anti-adhesion effect at 0.1 to 1.0% compared to the control group, and particularly at 1.0%, it was possible to almost completely prevent adhesion. This effect is 0.5 to 0.5 compared to known sodium hyaluronate
A good effect was shown at 1.0%.

Further, in the adhesion model used this time, similar evaluations were carried out on known sodium alginate, sodium chondroitin sulfate and dextran 70, and as a result, no adhesion prevention effect was recognized.

From the above, it has been clarified that xanthan gum has an excellent effect as an active ingredient of an intraabdominal adhesion preventive agent.

[0022]

INDUSTRIAL APPLICABILITY The agent for preventing intra-abdominal adhesion of the present invention can prevent intra-abdominal adhesion due to tissue dryness, bleeding, and tissue damage due to surgery during laparotomy. Therefore, postoperative intestinal adhesions and intestinal obstruction can be prevented, and the prognosis of postoperative patients can be kept good.

Claims (1)

[Claims] 1. An intraperitoneal adhesion preventive agent containing xanthan gum as an active ingredient.